Reports from our laboratory have shown that mice chronically infected with the protozoan parasite Toxoplasma gondii are remarkably resistant to the growth or development of a variety of autochthonous and transplantable tumors. The underlying mechanism of this nonspecific resistance appears to be the activated macrophages. Since approximately 50% of the adult population in the United States are already chronically infected with Toxoplasma and elicit a potent cell-mediated immune response (probably for life), the immunotherapeutic use of this organism or its antigens in the prevention or treatment of human cancer might be considered if further promising data in animals are made available. We propose to obtain such data through an in-depth study of Toxoplasma as an agent for both prevention of and therapy of established cancer in mice and to evaluate various strains and the effects of booster administration of Toxoplasma antigens in a variety of animal-tumor models. We will compare Toxoplasma immunotherapy with that employing Corynebacterium parvum and assess both forms of treatment in combination with established alternative therapeutic measures such as chemotherapy and radiotherapy.